ArticleJCI insight2018
Retinal de novo lipogenesis coordinates neurotrophic signaling to maintain vision.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- A catecholamine-independent pathway controlling adaptive adipocyte lipolysis.Nature metabolism · 2026Article
- Lipogenic enzyme FASN promotes mutant p53 accumulation and gain-of-function through palmitoylation.Nature communications · 2025Article
- Central activation of catecholamine-independent lipolysis drives the end-stage catabolism of all adipose tissues.bioRxiv : the preprint server for biology · 2024Article
- Upregulated hepatic lipogenesis from dietary sugars in response to low palmitate feeding supplies brain palmitate.Nature communications · 2024Article
- Increasing Energetic Demands on Photoreceptors in Diabetes Corrects Retinal Lipid Dysmetabolism and Reduces Subsequent Microvascular Damage.The American journal of pathology · 2023Article
- De novo lipogenesis fuels adipocyte autophagosome and lysosome membrane dynamics.Nature communications · 2023Article
- The Protective Effects of Neurotrophins and MicroRNA in Diabetic Retinopathy, Nephropathy and Heart Failure via Regulating Endothelial Function.Biomolecules · 2022Review
- Diminished retinal complex lipid synthesis and impaired fatty acid β-oxidation associated with human diabetic retinopathy.JCI insight · 2021Article
- Metabolite therapy guided by liquid biopsy proteomics delays retinal neurodegeneration.EBioMedicine · 2020Article
- New insights into the mechanisms of diabetic complications: role of lipids and lipid metabolism.Diabetologia · 2019Review
- Is Retinal Metabolic Dysfunction at the Center of the Pathogenesis of Age-related Macular Degeneration?International journal of molecular sciences · 2019Review
- NADAmerican journal of physiology. Endocrinology and metabolism · 2018Article
- Pyruvate kinase M2 isoform deletion in cone photoreceptors results in age-related cone degeneration.Cell death & disease · 2018Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Membrane lipid composition is central to the highly specialized functions of neurological tissues. In the retina, abnormal lipid metabolism causes severe forms of blindness, often through poorly understood neuronal cell death. Here, we demonstrate that deleting the de novo lipogenic enzyme fatty acid synthase (FAS) from the neural retina, but not the vascular retina, results in progressive neurodegeneration and blindness with a temporal pattern resembling rodent models of retinitis pigmentosa. Blindness was not rescued by protection from light-evoked activity; by eating a diet enriched in palmitate, the product of the FAS reaction; or by treatment with the PPARα agonist fenofibrate. Vision loss was due to aberrant synaptic structure, blunted responsiveness to glial-derived neurotrophic factor and ciliary neurotrophic factor, and eventual apoptotic cell loss. This progressive neurodegeneration was associated with decreased membrane cholesterol content, as well as loss of discrete n-3 polyunsaturated fatty acid- and saturated fatty acid-containing phospholipid species within specialized membrane microdomains. Neurotrophic signaling was restored by exogenous cholesterol delivery. These findings implicate de novo lipogenesis in neurotrophin-dependent cell survival by maintaining retinal membrane configuration and lipid composition, and they suggest that ongoing lipogenesis may be required to prevent cell death in many forms of retinopathy.
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Registered trials
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